Gennaro Lombardi started the business in 1897 as a grocery store at 53½ Spring Street, and began selling tomato pies wrapped in paper and tied with a string at lunchtime to workers from the area's factories. In 1905 Lombardi received a business license to operate a pizzeria restaurant, and soon had a loyal clientele, including Italian tenor Enrico Caruso. He later passed the business on to his son, George.[2]

In 1984, the original Lombardi's closed, but re-opened ten years later a block away at 32 Spring Street, run by Gennaro Lombardi III, Gennaro Lombardi's grandson, and his childhood friend John Brescio. This change in location and ten-year hiatus surrendered the title of America's oldest continuously operating pizzeria to Papa's Tomato Pies in Trenton, New Jersey, which opened in 1912 and has sold pies without interruption since.[3]

The relocated, reopened Lombardi's uses a coal oven to bake its pies the way the original did. It is unusual in not selling slices, highly popular throughout New York City. Only whole pies made to order are sold.

In 2005, Lombardi's offered entire pizzas for 5 cents, their 1905 price, to commemorate the 100th anniversary of the first pizza sold at its original location.